Neo-adjuvant Transarterial Chemoinfusion (TAI) for Patients With Hepatocellular Carcinoma Beyond Milan/UCSF Criteria Who Underwent Liver Transplantation

Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. Liver transplantation (LT) is the best curative treatment of HCC meeting Milan/UCSF criteria. Milan (solitary tumour <5cm, or up to 3 tumours, each <3cm) and University of California San Francisco (UCSF) criteria (solitary tumour ≤6.5cm, up to 3 tumours with none >4.5cm, and total tumour diameter ≤8cm) provide the benchmark requirements for LT, at which a 5-year survival of >70% and recurrence rate ranging from 5-15% can be achieved.

Recently, FOLFOX (Oxaliplatin and 5-fluorouracil) based hepatic artery infusion chemotherapy (HAIC) exhibited high response rate for advanced HCC. Neo-adjuvant TAI for the HCC patients with beyond criteria serving as a down-staging method for the advanced HCC to meet Milan/UCSF criteria，and qualify for LT.

This study is to compare the impact on survival of neo-adjuvant TAI for patients with beyond Milan/UCSF Criteria HCC who underwent LT.

Study Overview

• Status: Recruiting
• Conditions: Liver Transplantation; Hepatocellular Carcinoma
• Intervention / Treatment: Other: Transarterial chemoinfusion (TAI) with mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wenjie Zhang, PhD; Phone Number: +86136221584216; Email: drzhangwj@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Nanjing Drum Tower Hospital
      • Contact: Beicheng Sun, Phd,MD; Phone Number: +8613776413940; Email: sunbc@nju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. older than 18 years old and younger than 75 years listed for liver transplant;
2. ECOG PS≤1;
3. Child-Pugh Stage A or B
4. Proven hepatocellular carcinoma according patological examination or EASL/AASLD diagnostic criteria;
5. Not previous treated for tumor;
6. The tumor was diagnosed beyond Milan criteria or University of San Francisco criteria for LT
7. No distant metastasis;

8. The lab test could meet:

   Neutrophil count≥2.0×109/L; Hemoglobin≥100g/L; Platelet count≥75×109/L; Serum albumin≥35g/L; Total bilirubin<2-times upper limit of normal; ALT<3-times upper limit of normal; AST<3-times upper limit of normal; Serum creatine<1.5-times upper limit of normal; PT≤upper limit of normal plus 4 seconds; INR≤2.2;

9. Sign up consent.

Exclusion Criteria:

1. Cannot tolerate TAI or LT;
2. Distant metastasis exits;
3. Known history of other malignancy;
4. Be allergic to related drugs;
5. Be treated before (interferon included);
6. Known history of HIV infection;
7. Known history of drug or alcohol abuse;
8. Have GI hemorrhage or cardiac/brain vascular events within 30 days;
9. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: treatment group; Transarterial chemoinfusion (TAI) with mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU)	Other: Transarterial chemoinfusion (TAI) with mFOLFOX6 (oxaliplatin, calcium folinate, and 5-FU); TAI; Other Names: TAI
NO_INTERVENTION: control group; no neo-adjuvant treatment before operation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	From date of randomization until the date of death from any cause, assessed up to 60 months	From date of randomization until the date of death from any cause, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	recurrence-free survival	From date of randomization until the date of recurrence, assessed up to 60 months
recurrence rate	recurrence rate	1 year, 2 year, 3 year, 5 year after surgery
PFS	progression free survival	From date of randomization until the date of progression, assessed up to 60 months

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Study Chair: Beicheng Sun, PhD，MD, Nanjing University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2020
• Primary Completion (ANTICIPATED): November 30, 2024
• Study Completion (ANTICIPATED): October 30, 2026

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (ACTUAL): October 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: v1.0 20101014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No